Details of Drug-Drug Interaction
| Drug General Information (ID: DDIFUVCQ27) | |||||||||
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| Drug Name | Ritonavir | Drug Info | Edoxaban | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Anti-Hiv Agents | Anticoagulants/Factor Xa Inhibitors | |||||||
| Structure | |||||||||
| Mechanism of Ritonavir-Edoxaban Interaction (Severity Level: Major) | |||||||||
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| Transporter inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Ritonavir | Edoxaban | |||||||
| Mechanism | P-gp inhibitor | P-gp substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | P-glycoprotein 1 |
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Structure
Sequence
MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAIIHGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSGIGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVSKINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFTDKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSGQTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLFATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRSSLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAIINGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKAGEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEAIENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFGAYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDSYSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVVSQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTKRQ
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| Gene Name | ABCB1 | ||||||||
| Uniprot ID | MDR1_HUMAN | ||||||||
| KEGG Pathway | hsa:5243 | ||||||||
| Protein Family | ABC transporter superfamily | ||||||||
| Protein Function |
Translocates drugs and phospholipids across the membrane (PubMed:8898203, PubMed:2897240, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:9038218).
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | When used for the treatment of deep vein thrombosis and pulmonary embolism, the manufacturer recommends that edoxaban dosage be reduced to 30 mg once daily in patients receiving concomitant treatment with certain P-gp inhibitors including azithromycin, clarithromycin, erythromycin, oral itraconazole, oral ketoconazole, quinidine, and verapamil. This dosage recommendation is based on data from a clinical study, the Hokusai VTE study, and is limited to use with the specific P-gp inhibitors mentioned. Other P-gp inhibitors were not permitted in the study, and patients on antiretroviral therapy (ritonavir, nelfinavir, indinavir, saquinavir) as well as cyclosporine were excluded from the study. Following discontinuation of the P-gp inhibitor, edoxaban dosage should be returned to the regular dosage of 60 mg once daily. No dosage adjustment is recommended for edoxaban when used in the treatment of nonvalvular atrial fibrillation. | ||||||||